Why Does Acetazolamide Cause Hyperchloremic Metabolic Acidosis

Normal Anion Gap Metabolic Acidosis

Home | Critical Care Compendium | Normal Anion Gap Metabolic Acidosis Normal Anion Gap Metabolic Acidosis (NAGMA) HCO3 loss and replaced with Cl- -> anion gap normal if hyponatraemia is present the plasma [Cl-] may be normal despite the presence of a normal anion gap acidosis -> this could be considered a ‘relative hyperchloraemia’. Extras – RTA, ingestion of oral acidifying salts, recovery phase of DKA loss of bicarbonate with chloride replacement -> hyperchloraemic acidosis secretions into the large and small bowel are mostly alkaline with a bicarbonate level higher than that in plasma. some typical at risk clinical situations are: external drainage of pancreatic or biliary secretions (eg fistulas) this should be easily established by history normally 85% of filtered bicarbonate is reabsorbed in the proximal tubule and the remaining 15% is reabsorbed in the rest of the tubule in patients receiving acetazolamide (or other carbonic anhydrase inhibitors), proximal reabsorption of bicarbonate is decreased resulting in increased distal delivery and HCO3- appears in urine this results in a hyperchloraemic metabolic acidosis and is essentially a form of proximal renal tubular acidosis but is usually not classified as such. hyperchloraemic metabolic acidosis commonly develops during therapy of diabetic ketoacidosis with normal saline oral administration of CaCl2 or NH4Cl is equivalent to giving an acid load both of these salts are used in acid loading tests for the diagnosis of renal tubular acidosis CaCl2 reacts with bicarbonate in the small bowel resulting in the production of insoluble CaCO3 and H+ the hepatic metabolism of NH4+ to urea results in an equivalent production of H+ REASONS WHY ANION GAP MAY BE NORMAL DESPITE A ‘HIGH ANION GAP METABOLIC ACIDOSIS’ 1.
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Acetazolamide [tusom | Pharmwiki]

Trade Names: generic, Diamox, Diamox Sequels Drug Class: diuretic (carbonic anhydrase inhibitor) The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of bicarbonate (HCO3 ion), which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are the end result. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization. Carbonic anhydrase inhibitors were the forerunners of modern diuretics. Legend. Mechanism of action of carbonic anhydrase inhibitor diuretics. Bicarbonate absorption by the proximal tubule is dependent on the activity of carbonic anhydrase (CA) which converts bicarbonate (HCO3-) to CO2 and H2O. CO2 rapidly diffuses across the cell membrane of proximal tubule cells where it is rehydrated back to H2CO3 by carbonic anhydrase. H2CO3 dissociates to HCO3- and H+ which are transported out of the cell on the basolateral side by different transporters. Bicarbonate absorption is therefore dependent on the activity of carbonic anhydrase. Inhibition of carbonic anhydrase by acetazolamide results in an increased urinary loss of bicarbonate. This also interferes with the reabsorption of Na and Cl. The basolateral Na/K ATPase (found in most epithelial cells lining the nephron) maintains a low intracellular Na concentration, which is necessary for reabsorption of Na, and in the proximatl tubule also facilitates the efflux of H+ by the Na/H exchanger on the luminal side. Increased delivery of Na to the collecting duct results in reabsorption of Na (through epithelial Na channels) in exchange for increased K efflux
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Hyperchloremic Acidosis

Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP more... This article covers the pathophysiology and causes of hyperchloremic metabolic acidoses , in particular the renal tubular acidoses (RTAs). [ 1 , 2 ] It also addresses approaches to the diagnosis and management of these disorders. A low plasma bicarbonate (HCO3-) concentration represents, by definition, metabolic acidosis, which may be primary or secondary to a respiratory alkalosis. Loss of bicarbonate stores through diarrhea or renal tubular wasting leads to a metabolic acidosis state characterized by increased plasma chloride concentration and decreased plasma bicarbonate concentration. Primary metabolic acidoses that occur as a result of a marked increase in endogenous acid production (eg, lactic or keto acids) or progressive accumulation of endogenous acids when excretion is impaired by renal insufficiency are characterized by decreased plasma bicarbonate concentration and increased anion gap without hyperchloremia. The initial differentiation of metabolic acidosis should involve a determination of the anion gap (AG). This is usually defined as AG = (Na+) - [(HCO3- + Cl-)], in which Na+ is plasma sodium concentration, HCO3- is bicarbonate concentration, and Cl- is chloride concentration; all concentrations in this formula are in mmol/L (mM or mEq/L) (see also the Anion Gap calculator). The AG value represents the difference between unmeasured cations and anions, ie, the presence of anions in the plasma that are not routinely measured. An increased AG is associated with renal failure, ketoacidosis, lactic acidosis, and ingestion of certain toxins. It can usually be easily identified by evaluating routine plasma chemistry results and from the clinical picture. A normal AG
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Can Acetazolamide Cause Hyperchloraemia?

Lamisil vs Lotrimin Mucinex vs Sudafed Lactogen 1 Side Effects Evekeo vs Adderall Dexilant and Alcohol Treato does not review third-party posts for accuracy of any kind, including for medical diagnosis or treatments, or events in general. Treato does not provide medical advice, diagnosis or treatment. Usage of the website does not substitute professional medical advice. The side effects featured here are based on those most frequently appearing in user posts on the Internet. The manufacturer's product labeling should always be consulted for a list of side effects most frequently appearing in patients during clinical studies. Talk to your doctor about which medications may be most appropriate for you. The information reflected here is dependent upon the correct functioning of our algorithm. From time-to-time, our system might experience bugs or glitches that affect the accuracy or correct application of mathematical algorithms. We will do our best to update the site if we are made aware of any malfunctioning or misapplication of these algorithms. We cannot guarantee results and occasional interruptions in updating may occur. Please continue to check the site for updated information.
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Diuretics Flashcards | Quizlet

- Osmotic diuretics (mannitol, glucose): promote water retention in the tubular fluid - Other diuretics (loops, thiazides, etc): 'natiuretics' that interfere with active or passive uptake of sodium How is sodium bicarbonate absorption regulated in the proximal tubule? How about Na+? o Proximal tubule: sodium bicarbonate reabsorption by the proximal tubule is initiated by the action of the Na+/H+ exchanger NHE3, which allows Na+ to enter the cell. The transport of Na+ is dependent upon H+ produced through carbonic anhydrase Acetazolamide: carbonic anhydrase inhibitor; leads to blocking of sodium bicarbonate reabsorption, resulting in a decrease in sodium chloride reabsorption; causes urine pH to rise and can cause blood pH to fall How does acetazolamide affect urine and plasma pH Acetazolamide: carbonic anhydrase inhibitor; leads to blocking of sodium bicarbonate reabsorption, resulting in a decrease in sodium chloride reabsorption; causes urine pH to rise and can cause blood pH to fall What are the pharmacokinetics of acetazolamide? Pharmacokinetics: well absorbed after oral administration; inhibits carbonic anhydrase in proximal and late distal tubule; excretion of drug is by tubular secretion in proximal tubule (if you use too much diuretic like acetazolamide you can have too concentrated urine because the active transport mechanisms used for acetazolamide secretion are also used for urea secretion, without enough urea in the lumen you can't bring as much water in to dilute Pharmacokinetics: well absorbed after oral administration; inhibits carbonic anhydrase in proximal and late distal tubule; excretion of drug is by tubular secretion in proximal tubule (if you use too much diuretic you can have too concentrated urine because the active transport mechanisms used for
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Acetazolamide/Acetazolamide Sodium/Diamox Intravenous Inj Pwd F/Sol: 500mg Acetazolamide/Diamox Oral Tab: 125mg, 250mg Acetazolamide/Diamox/Diamox Sequels Oral Cap ER: 500mg For the adjunctive treatment of open-angle glaucoma. 250 mg PO given 1 to 4 times daily. Maintenance dosage should be titrated to response. The maximum dosage is 1 g/day. Consider dosage reduction. An elderly patient is more likely to develop hyperchloremic metabolic acidosis in addition to an age-related renal impairment. 8 to 30 mg/kg/day PO or 300 to 900 mg/m2/day, given in divided doses every 8 hours. 5 to 10 mg/kg IV every 6 hours for acute glaucoma. Maximum dosage is 1 g/day. For use as an alternative agent in the treatment of absence seizures. NOTE: The extended release preparation is not recommended for use as an anticonvulsant. Oral dosage (regular-release tablets only) 8 to 30 mg/kg/day PO, given in up to 4 divided doses. The usual maintenance dosage is 375 to 1,000 mg/day. Consider dosage reduction. An elderly patient is more likely to develop hyperchloremic metabolic acidosis in addition to an age-related renal impairment. 8 to 30 mg/kg/day IV, given in up to 4 divided doses. The usual maintenance dosage is 375 to 1,000 mg/day. Consider dosage reduction. An elderly patient is more likely to develop hyperchloremic metabolic acidosis in addition to an age-related renal impairment. For the treatment of acute altitude sickness. 250 mg PO twice daily is recommended by clinical practice guidelines. Descent is the preferred initial treatment. When descent is not possible or effective, symptomatic treatment (e.g., analgesics and antiemetics), oxygen, and other treatments, including acetazolamide, should be considered. The FDA-approved dosage is 500 to 1,000 mg PO daily, in divided doses, for 48
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Acetazolamide - Pharmapedia

Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, benign intracranial hypertension (pseudotumor cerebri), altitude sickness, cystinuria, and dural ectasia. Acetazolamide is available as a generic drug and is also used as a diuretic. This section may be confusing or unclear to readers. Please help clarify the article; suggestions may be found on the talk page. (June 2009) This drug is a carbonic anhydrase inhibitor. Carbonic anhydrase (CA) catalyzes the forward motion of molecules in the following equation: where CA converts carbon dioxide (CO2) and water (H2O) to carbonic acid (H2CO3), which then dissociates to a hydrogen ion (H+, an acidic proton), and a bicarbonate ion (HCO3-, a basic anion). In some tissues (particularly plants), the equilibrium is such that CA can catalyze the reverse direction of the reaction. Carbonic acid inhibitors, such as acetazolamide, inhibit CA in tissue and fluid, causing less movement of carbonic acid toward CO2 production. In the kidneys, blocking CA leads to bicarbonate wasting in the tubules (alkalizes urine), loss of bicarbonate subsequently leads to a metabolic acidosis. In the meantime, H+ backs up due to acetazolamide CA inhibition in the tubule and enters the cell with Cl-, then passes into the bloodstream, creating a hyperchloremic metabolic acidosis.[1] This effect can also be used for therapeutic correction of respiratory alkalosis. Acetazolamide is often used in the treatment of various diseases. It has been used for glaucoma sufferers.[2] The drug decreases fluid formation in the eye resulting in lower intraocular pressure. In epilepsy, its main use is in absence seizures and myoclonic seizures.[3] It is also used to decrease generation of c
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Acetazolamide: Mechanism Of Action

Home / ABA Keyword Categories / A / Acetazolamide: mechanism of action Acetazolamide is a reversible inhibitor of the carbonic anhydrase enzyme that results in reduction of hydrogen ion secretion at the renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water. It can be used as a diuretic or to treat glaucoma as it prevents excessive build up of aqueous humor. It also inhibits carbonic anhydrase in the central nervous system to minimize abnormal and excessive discharge from CNS neurons. Acetazolamide can be administered to patients with a metabolic alkalosis to promote retention of hydrogen ions at the level of the renal tubule. Mechanism of action: for the reduction of Intraocular pressure Acetazolamide inactivates carbonic anhydrase and interferes with the sodium pump, which decreases aqueous humor formation and thus lowers IOP. Systemic effects however include increased renal loss of sodium, potassium, and water secondary to the drugs renal tubular effects. Arterial Blood gases may show a mild hyperchloremic metabolic acidosis.
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Drug-induced Metabolic Acidosis

Go to: Introduction Metabolic acidosis is defined as an excessive accumulation of non-volatile acid manifested as a primary reduction in serum bicarbonate concentration in the body associated with low plasma pH. Certain conditions may exist with other acid-base disorders such as metabolic alkalosis and respiratory acidosis/alkalosis 1. Humans possess homeostatic mechanisms that maintain acid-base balance ( Figure 1). One utilizes both bicarbonate and non-bicarbonate buffers in both the intracellular and the extracellular milieu in the immediate defense against volatile (mainly CO 2) and non-volatile (organic and inorganic) acids before excretion by the lungs and kidneys, respectively. Renal excretion of non-volatile acid is the definitive solution after temporary buffering. This is an intricate and highly efficient homeostatic system. Derangements in over-production, under-excretion, or both can potentially lead to accumulation of excess acid resulting in metabolic acidosis ( Figure 1). Drug-induced metabolic acidosis is often mild, but in rare cases it can be severe or even fatal. Not only should physicians be keenly aware of this potential iatrogenic complication but they should also be fully engaged in understanding the pathophysiological mechanisms. Metabolic acidosis resulting from drugs and/or ingestion of toxic chemicals can be grouped into four general categories ( Figure 2): Some medications cannot be placed into one single category, as they possess multiple mechanisms that can cause metabolic acidosis. In suspected drug-induced metabolic acidosis, clinicians should establish the biochemical diagnosis of metabolic acidosis along with the evaluation of respiratory compensation and whether there is presence of mixed acid-based disorders 2, then convert the bioche
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Acid-base Physiology

8.4.1 Is this the same as normal anion gap acidosis? In hyperchloraemic acidosis, the anion-gap is normal (in most cases). The anion that replaces the titrated bicarbonate is chloride and because this is accounted for in the anion gap formula, the anion gap is normal. There are TWO problems in the definition of this type of metabolic acidosis which can cause confusion. Consider the following: What is the difference between a "hyperchloraemic acidosis" and a "normal anion gap acidosis"? These terms are used here as though they were synonymous. This is mostly true, but if hyponatraemia is present the plasma [Cl-] may be normal despite the presence of a normal anion gap acidosis. This could be considered a 'relative hyperchloraemia'. However, you should be aware that in some cases of normal anion-gap acidosis, there will not be a hyperchloraemia if there is a significant hyponatraemia. In a disorder that typically causes a high anion gap disorder there may sometimes be a normal anion gap! The anion gap may still be within the reference range in lactic acidosis. Now this can be misleading to you when you are trying to diagnose the disorder. Once you note the presence of an anion gap within the reference range in a patient with a metabolic acidosis you naturally tend to concentrate on looking for a renal or GIT cause. 1. One possibility is the increase in anions may be too low to push the anion gap out of the reference range. In lactic acidosis, the clinical disorder can be severe but the lactate may not be grossly high (eg lactate of 6mmol/l) and the change in the anion gap may still leave it in the reference range. So the causes of high anion gap acidosis should be considered in patients with hyperchloraemic acidosis if the cause of the acidosis is otherwise not apparent.
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How Does Acetazolamide Cause Hyperchloremia?

SDN members see fewer ads and full resolution images. Join our non-profit community! how does acetazolamide cause hyperchloremia? I'm trying to figure out why (mechanism). Acidosis makes sense, and so does hypokalemia. Thanks. I think it's because carbonic anhydrase inhibitors prevent HCO3 reabsorption, so more sodium is being excreted as NaHCO3 instead of NaCl. every non-anion gap acidosis has hyperchloremia. it's inevitable, and unimportant It causes a non-anion gap metabolic acidosis. As the negative bicarb is ridded by the kidney, another anion needs to fill its place in the serum, and this is done by Cl. What makes sense to me, but I could be totally wrong is: Acidosis stimulates the release of aldosterone -> increase in activity of NaCl Cotransporter in early DCT-> Hyperchloremia Pretty sure Aldo isn't involved in the NCC. What the others have said is correct. What makes sense to me, but I could be totally wrong is: Acidosis stimulates the release of aldosterone -> increase in activity of NaCl Cotransporter in early DCT-> Hyperchloremia Lol, sorry to pick on you, but you couldn't be more wrong. I don't think there's one correct statement in there.
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Comments On Diuretics

which I understand acetazolamide does not cause inc chloride in the blood...It cause hyperchlormic metabolic acidosis ,not hyperchloremia... mechanesim of hyperchloremic metabolic acidosis...CA (present in ptubuler epithelium of proximal convoluted epithelium)catalyzes the reaction of CO2+ H2O =H2CO3 both in epithelial cell of renal tubules and lumen as well..after formation of H2CO3 (in epithelial cell)it degrade in to Hydrogen ion and Hco3-(bicarbonate) which enter in to the blood while H+ enter in to the lumen with exchange of Na with this mechanism Na will enter in to the blood ...the H ion which enter with exchange of Na is then react with lumenal HCO3- and forn H2CO3 which then form H2) and CO2 in lumen If CA inhibited by acetazolamide this reaction will not produce H+ for Na exchange ..result in mild diuresis while(luminal) HCO3- retained in the lumen (because there is no H ion available for the formation of H2CO3)..this retained HCO3- will increases the urinary pH and loss in the urine ..this loss cause a hyperchloremic metabolic acidosis
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